For manufacturers of parenteral fluids who wish to replace the traditional glass containers, it has been a highly demanding problem to find a polymeric material capable of withstanding autoclavation and yet be able to meet the often rigorous requirements set on its oxygen barrier and water vapor barrier capacities. Especially when sensitive fluids for use in parenteral nutrition, such as lipid emulsions containing long chain polyunsaturated fatty acids, amino acid solutions and carbohydrates shall be heat sterilized and stored for a long time, problems with oxygen induced degradation and incompatibility with the polymeric material, might lead to the appearance of potentially hazardous products. A solution to the problem of finding a suitable storage system comprising a flexible container filled with parenteral nutrients to replace glass bottles is demonstrated in the as yet unpublished Swedish patent application 9601348-7.
When manufacturing different types of containers of polymeric materials for storing parenterally administerable fluids, it has been a considerable problem to provide a suitable degree of sterility for all the parts of the container. It would also be highly desirable, for reasons of safety for the patients, for the convenience of hospital personal and for economical reasons to achieve and maintain a suitably high degree of sterility by means of a single steam sterilization process (i.e. autoclavation) which is performed after the container has been finally assembled, filled and scaled.
Flexible containers for storage of parenteral nutrients are conventionally provided with ports for filling and dispensing of the nutrients. Tubular ports may be attached by means of welding when forming side seams, as performed in the International Patent Application WO 95/26177 (Fresenius AG). Another manner of providing a flexible container with ports is disclosed in the above mentioned Swedish patent application 9601348-7, wherein a flexible polymer material is introduced in the form of sheets, to which a saddle formed port system comprising two separate ports is attached. When manufacturing such a container two holes are pressed in the sheet for the tubular ports, whereupon the saddle is welded to the sheet which is folded and welded to a bag shaped container by forming two side seams and a top seam. The container may be filled through the saddle formed port, or preferably by one or more temporary ports in connection to the welded seams before it is sterilized.
Conventional saddle-formed port systems normally comprise an additive port for the introduction to the container, just before administration, of a complementary perishable fluid, such as a solution of vitamins to a stored parenteral nutrient. It will also comprise a dispensing port for establishing a fluid connection between the container and the patient in need of fluid therapy. The ports are generally tube formed and often of a predetermined different size in order to clearly show their identity to the user.
The additive port is often sealed with a stopper made of latex rubber fitted in mouth of the port which can be penetrated by a needle. The dispensing port is typically formed with a membrane of polypropylene which can be pierced with a spike connected to the infusion device. The mouth of such a port is finally sealed before storage by a removable cap or a foil. These ports have a drawback in that the small space between the stopper and the sealing cap or foil will not be reached by sterilizing steam which constitutes a risk for contamination in connection with the penetration. To solve this problem, the saddle-formed port systems have either been pre-sterilized by means of radiation before being assembled to the bags or alternatively a water droplet has been introduced in the small space to provide sterilizing vapor during the heat treatment. Both these solutions are unsatisfying, since they require either an extra sterilization routine by radiation which often might deteriorate the quality of polymeric materials or an extra water droplet adding routine. Whenever using this type of container, handling personnel at hospitals are instructed to, as an extra safety routine, wipe the latex rubber with a disinfectant before piercing it with a needle connected to an infusion tubing.
The same problem is also present with the type of plastic bottle formed containers made with a "blow-fill-seal" method, as described in the Swedish patent application 9303123-5. This type of bottles are sealed by a resilient stopper and a cap at the top of the bottle and finally sealed in the autoclave with a weak seal between the stopper and the inner surface of the container neck. The small space between the stopper and the cap will not be properly sterilized by steam unless a water droplet is introduced in a separate process. An incorrectly sterilized pierceable surface means a risk for contamination, especially when the containers are aimed for storage of several dosages and several collections of fluid will be made by piercing the stopper with a needle.
It would also be highly desirable to be able to recycle also a bag-formed container with an attached saddle-formed port system without a laborious dismembering and collection of different materials in separate processes, as being made possible with the containers, according to the mentioned the Swedish patent application 9303123-5. The frequently used resilient latex stopper of the ports must be individually collected from used bags before they can be recycled. The presence of any latex stoppers will effectively spoil a recycling process of polypropylene based bags. It would also be advantageous to benefit from the advantage of introducing sealing weak weldings with the final heat sterilization, as obtained between the container body or the cap and elastomeric sealing device in the mentioned Swedish patent application 9303123-5.
It would also be desirable to provide a saddle formed port system having ports which fit to high number of spike connections without leakage so they are compatible with a large number of infusion sets existing on the market. Dispensing ports sealed with a polypropylene membrane, in particular will often leak and are not sufficiently resealable after being pierced. On the other hand, latex stoppers in addition ports have a drawback in their tendency to be unintentionally displaced from the mouth of the port. This type of sealing device might also cause problems due to particles torn off when being penetrated